To determine: 1) what physiologic or pharmacologic events or chemicals influence pressure relationships between the duodenum and pancreatic duct which might favor reflux of duodenal contents into the pancreatic duct; and 2) if carcinogens can reflux from the duodenum into the pancreatic duct and induce pancreatic carcinogenesis, we have established a canine model. In the past year we have: 1) demonstrated that during fasting pancreatic and biliary secretion into the duodenum are cyclic and associated with interdigestive motor activity; 2) detected small amounts of duodenally perfused marker within the pancreatic duct in a minority of dogs during fasting; 3) determined that hormones (secretin and cholecystokinin/octapeptide) maintain or cause a fall in the pancreatic duct pressure to duodenal pressure gradient; 4) demonstrated that nicotine diminishes the cycling time of both the secretory and motor component of the interdigestive motor complex; and 5) in preliminary studies found that 14C-benzanthracene is secreted into the gastrointestinal tract cyclically in concert with the secretory and motor cycles of the interdigestive motor complex. These preliminary results suggest a link between cigarette smoking and pancreatic carcinogenesis. If carcinogens are cyclically secreted into the gastrointestinal tract in concert with gastrointestinal motor and secretory activity and nicotine diminishes cycling time, nicotine may increase exposure of the gastrointestinal tract to carcinogens.